Thrombolysis for Ischemic Stroke Beyond the 4.5-Hour Window: A Meta-Analysis of Randomized Clinical Trials.

IF 7.8 1区医学 Q1 CLINICAL NEUROLOGY

Stroke Pub Date : 2025-03-01 Epub Date: 2025-01-30 DOI:10.1161/STROKEAHA.124.048536

Ahmet Günkan, Marcio Yuri Ferreira, Marina Vilardo, Luca Scarcia, Jhon E Bocanegra-Becerra, Leonardo Januario Campos Cardoso, Luis F Fabrini Paleare, Gustavo de Oliveira Almeida, Gabriel Semione, Christian Ferreira, Gabriele Ciccio, Adnan Mujanovic, Pascal Jabbour, Yafell Serulle, Thanh N Nguyen, Jean-Claude Baron

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引用次数: 0

Abstract

Background: A minority of patients with stroke qualify for intravenous thrombolysis (IVT) within 4.5-hour window. The safety and efficacy of IVT beyond this period have not been well studied.

Methods: We systematically searched MEDLINE, Embase, Cochrane, and ClinicalTrials.gov for relevant randomized clinical trials. Randomized clinical trials comparing IVT versus standard medical care in patients with ischemic stroke beyond 4.5 hours of symptom onset or last known well without mechanical thrombectomy (MT) were included. Primary outcomes were excellent (modified Rankin Scale score of 0-1) and good (modified Rankin Scale score of 0-2) functional outcomes at 90 days, symptomatic intracerebral hemorrhage (sICH), and death at 90 days. Pooled odds ratios (ORs) with 95% CIs were calculated using a random-effects model. Heterogeneity was assessed by Q test and quantified by I² values.

Results: Eight randomized clinical trials (1742 patients; mean age, 69.8±9 years, 63.5% men) were included. Compared with standard medical care, IVT achieved higher rates of excellent (OR, 1.43 [95% CI, 1.17-1.75]; Q=2.30; P=0.94; I²=0%) and good functional outcomes (OR, 1.36 [95% CI, 1.12-1.66]; Q=2.07; P=0.96; I²=0%) at 90 days but also increased sICH rates (OR, 4.25 [95% CI, 1.67-10.84], Q=0.48; P=0.99; I²=0%). Mortality at 90 days did not significantly differ between treatment groups (OR, 1.28 [95% CI, 0.87-1.89]; Q=4.63; P=0.59; I²=0%). Subanalyses yielded numerically higher odds of excellent functional outcomes when patients were selected with perfusion imaging (3 studies, OR, 1.45 [95% CI, 1.08-1.94]) compared with diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch (3 studies, OR, 1.34 [95% CI, 0.94-1.91]) and when treated with tenecteplase (3 studies, OR, 1.47 [95% CI, 1.06-2.04]) compared with alteplase (5 studies, OR, 1.38 [95% CI, 1.08-1.78]).

Conclusions: IVT for ischemic stroke beyond 4.5 hours, without MT, led to increased odds of excellent and good functional outcomes compared with standard medical care, despite higher odds of sICH, and a nonsignificant numerical increase in mortality.

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超过4.5小时窗期的缺血性卒中溶栓治疗：随机临床试验的荟萃分析

背景：少数脑卒中患者有资格在4.5小时内静脉溶栓（IVT）。IVT超过这一时期的安全性和有效性尚未得到很好的研究。方法：系统地检索MEDLINE、Embase、Cochrane和ClinicalTrials.gov，查找相关的随机临床试验。随机临床试验比较IVT与标准医疗护理的缺血性卒中患者超过4.5小时症状发作或最后一次知道没有机械取栓（MT）。主要结局为90天功能结局优秀（改良Rankin评分0-1分）和良好（改良Rankin评分0-2分），90天症状性脑出血（siich）和死亡。采用随机效应模型计算95% ci的合并优势比（or）。异质性采用Q检验，I²值量化。结果：8项随机临床试验(1742例患者；平均年龄（69.8±9岁），男性63.5%。与标准医疗护理相比，IVT获得更高的优良率(OR, 1.43 [95% CI, 1.17-1.75]；Q = 2.30;P = 0.94;I2=0%)和良好的功能结局(OR, 1.36 [95% CI, 1.12-1.66]；Q = 2.07;P = 0.96;I2=0%)，但也增加了脑出血发生率(OR, 4.25 [95% CI, 1.67-10.84]， Q=0.48；P = 0.99;I2 = 0%)。治疗组90天死亡率无显著差异(OR, 1.28 [95% CI, 0.87-1.89]；Q = 4.63;P = 0.59;I2 = 0%)。亚分析结果显示，当患者选择灌注成像（3项研究，OR为1.45 [95% CI, 1.08-1.94]）与扩散加权成像-液体衰减反演恢复失配（3项研究，OR为1.34 [95% CI, 0.94-1.91]）相比，当患者选择替奈普酶（3项研究，OR为1.47 [95% CI, 1.06-2.04]）与阿替普酶（5项研究，OR为1.38 [95% CI, 1.08-1.78]）相比，获得优异功能结果的几率更高。结论：IVT治疗超过4.5小时的缺血性卒中，不进行MT治疗，与标准医疗护理相比，尽管siich的几率更高，死亡率的数值增加不显著。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stroke 医学-临床神经学

CiteScore

13.40

自引率

6.00%

发文量

2021

审稿时长

3 months

期刊介绍： Stroke is a monthly publication that collates reports of clinical and basic investigation of any aspect of the cerebral circulation and its diseases. The publication covers a wide range of disciplines including anesthesiology, critical care medicine, epidemiology, internal medicine, neurology, neuro-ophthalmology, neuropathology, neuropsychology, neurosurgery, nuclear medicine, nursing, radiology, rehabilitation, speech pathology, vascular physiology, and vascular surgery. The audience of Stroke includes neurologists, basic scientists, cardiologists, vascular surgeons, internists, interventionalists, neurosurgeons, nurses, and physiatrists. Stroke is indexed in Biological Abstracts, BIOSIS, CAB Abstracts, Chemical Abstracts, CINAHL, Current Contents, Embase, MEDLINE, and Science Citation Index Expanded.